DIFFERENTIAL-EFFECTS OF EICOSAPENTAENOIC ACID ON GLYCEROLIPID AND APOLIPOPROTEIN-B METABOLISM IN PRIMARY HUMAN HEPATOCYTES COMPARED TO HEPG2 CELLS AND PRIMARY RAT HEPATOCYTES
DIFFERENTIAL-EFFECTS OF EICOSAPENTAENOIC ACID ON GLYCEROLIPID AND APOLIPOPROTEIN-B METABOLISM IN PRIMARY HUMAN HEPATOCYTES COMPARED TO HEPG2 CELLS AND PRIMARY RAT HEPATOCYTES
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DOI：
10.1016/0005-2760(95)00006-x
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发表时间：
1995-04-28
期刊：
影响因子：
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通讯作者：
KUIPERS, F
中科院分区：
文献类型：
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作者：
LIN, YG;SMIT, MJ;KUIPERS, F
我们比较了二十碳五烯酸（EPA）和油酸（OA）对原代人肝细胞、HepG 2细胞和原代大鼠肝细胞中甘油脂质和载脂蛋白B（apo B）代谢的影响。在不存在（对照）或存在ImM EPA或OA的情况下，将细胞与0.25mM牛血清白蛋白一起孵育1至5小时。在与[H-3]甘油孵育1小时后测定[H-3]甘油酯的合成和分泌。通过蛋白质印迹法半定量估计人细胞中的细胞和培养基apoB丰度。提出了以下意见。(1)与对照组相比，OA诱导人肝细胞中[H-3]三酰甘油（TG）合成增加7倍，大鼠肝细胞和HepG 2细胞中增加4倍。EPA在所有三种细胞类型中增强[H-3]TG合成约2倍，尽管它在一定程度上刺激[H-3]二酰基甘油（DG）合成（即，2.5-5倍）与OA相似。(2)与OA相比，EPA在三种细胞类型中刺激VLDL相关的[H-3]TG分泌2.5至3倍，EPA在HepG 2和大鼠肝细胞中不改变[H-3]TG分泌，并在原代人肝细胞中抑制[H-3]TG分泌75%。(3)在原代人肝细胞中，OA和EPA都没有改变细胞apoB丰度，但EPA与对照相比使apoB分泌减少44%。相比之下，EPA和OA都增加了HepG 2细胞中细胞和培养基apoB的丰度2至2.5倍，尽管在EPA处理的细胞中培养基apoB倾向于较低。(4)EPA对大鼠肝细胞中[H-3]磷脂酰胆碱（PC）的合成没有影响，但在人肝细胞和HepG 2细胞中使[H-3]PC的合成降低了30%。该研究表明，在原代人肝细胞中，EPA通过影响VLDL颗粒组装和/或分泌将TG分泌降低至低于对照值。EPA和OA对原代人肝细胞与HepG 2和原代大鼠肝细胞（两种最常用的体外研究肝脂质代谢的模型系统）之间的甘油脂质和apoB代谢的影响存在定性和定量差异。
We compared the effects of eicosapentaenoic acid (EPA) and oleic acid (OA) on glycerolipid and apolipoprotein B (apoB) metabolism in primary human hepatocytes, HepG2 cells and primary rat hepatocytes. Cells were incubated for 1 to 5 h with 0.25 mM bovine serum albumin in the absence (control) or presence of 1 mM of EPA or OA. Synthesis and secretion of [H-3]glycerolipid were determined after 1 h incubation with [H-3]glycerol. Cellular and medium apoB abundance was semi-quantitatively estimated in human cells by Western blotting. The following observations were made. (1) Compared to control, OA induced a 7-fold increase in [H-3]triacylglycerol (TG) synthesis in human hepatocytes and a 4-fold increase in rat hepatocytes and HepG2 cells. EPA enhanced [H-3]TG synthesis about 2-fold in all three cell types although it stimulated [H-3]diacylglycerol (DG) synthesis to an extent (i.e., 2.5- to 5-fold) similar to OA. (2) In contrast to OA, which stimulated VLDL-associated [H-3]TG secretion 2.5- to 3-fold in the three cell types relative to control, EPA did not alter [H-3]TG secretion in HepG2 and rat hepatocytes and suppressed [H-3]TG secretion by 75% in primary human hepatocytes. (3) In primary human hepatocytes, both OA and EPA did not alter cellular apoB abundance but EPA decreased apoB secretion by 44% as compared to control. In contrast, both EPA and OA increased cellular and medium apoB abundance 2- to 2.5-fold in HepG2 cells, although medium apoB tended to be lower in EPA-treated cells. (4) EPA had no effect on the [H-3]phosphatidylcholine (PC) synthesis in rat hepatocytes, but decreased [H-3]PC synthesis by 30% in human hepatocytes and HepG2 cells. This study shows that, in primary human hepatocytes, EPA decreases TG secretion below control Values by influencing VLDL particle assembly and/or secretion. There are both qualitative and quantitative differences in the effects of EPA and OA on the glycerolipid and apoB metabolism between primary human hepatocytes and both HepG2 and primary rat hepatocytes, the two most commonly used model systems to investigate hepatic lipid metabolism in vitro.